Introduction
Vamorolone (VBP15) is a novel dissociative steroidal anti-inflammatory medication that represents a significant advancement in corticosteroid therapy. Developed as a potential treatment for Duchenne muscular dystrophy (DMD), vamorolone offers anti-inflammatory benefits while potentially mitigating the traditional steroid-related side effects that have limited long-term corticosteroid use in chronic conditions.
Mechanism of Action
Vamorolone functions as a dissociative steroid that binds to glucocorticoid receptors but modulates transcriptional activity differently than conventional corticosteroids. Unlike traditional glucocorticoids that activate both transactivation and transrepression pathways, vamorolone preferentially activates anti-inflammatory transrepression pathways while minimizing the transactivation pathways associated with many steroid-related adverse effects. This unique mechanism provides the anti-inflammatory benefits of corticosteroids while potentially reducing metabolic, endocrine, and bone-related side effects.
Indications
Vamorolone is FDA-approved for the treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older. Clinical trials have demonstrated its efficacy in improving motor function and slowing disease progression in ambulatory patients with DMD. Research is ongoing regarding its potential application in other inflammatory and autoimmune conditions where long-term steroid therapy is indicated.
Dosage and Administration
The recommended dosage for DMD is 6 mg/kg/day administered orally once daily with food. The medication is available as an oral suspension (40 mg/mL). Dosage adjustments may be necessary based on clinical response and tolerability. For patients with hepatic impairment, dosage reduction may be required. No specific dosage adjustments are recommended for renal impairment or geriatric patients, though clinical monitoring is advised.
Pharmacokinetics
Absorption: Vamorolone is well absorbed orally with a time to peak concentration (Tmax) of approximately 2-4 hours. Administration with food increases bioavailability. Distribution: The drug is extensively distributed throughout body tissues with a volume of distribution of approximately 100 L. Protein binding is approximately 97%, primarily to albumin. Metabolism: Vamorolone undergoes extensive hepatic metabolism primarily via CYP3A4 enzymes, with minor contributions from other CYP enzymes. Elimination: The elimination half-life is approximately 4-6 hours. Excretion occurs primarily through feces (approximately 70%) with lesser amounts eliminated in urine (approximately 20%).Contraindications
Vamorolone is contraindicated in patients with:
- Known hypersensitivity to vamorolone or any component of the formulation
- Systemic fungal infections
- Live or attenuated virus vaccinations during treatment
Warnings and Precautions
Immunosuppression: Increased susceptibility to infections, including serious and sometimes fatal infections. Monitor patients for infection during and after treatment. Adrenal suppression: May occur with prolonged therapy; taper dose gradually when discontinuing treatment. Ophthalmic effects: May cause cataracts, glaucoma, and corneal thinning; regular ophthalmologic examinations recommended. Cardiovascular effects: May cause hypertension and fluid retention; monitor blood pressure and weight regularly. Gastrointestinal effects: Increased risk of gastrointestinal perforation in patients with certain GI disorders. Behavioral and mood changes: May cause psychiatric disturbances including emotional lability, euphoria, and depression. Vaccinations: Avoid live vaccines during treatment; killed or inactivated vaccines may be administered.Drug Interactions
Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin): May increase vamorolone exposure; consider dosage reduction Strong CYP3A4 inducers (e.g., rifampin, carbamazepine): May decrease vamorolone exposure; monitor efficacy Anticoagulants: May potentiate effects of warfarin; monitor INR closely Antidiabetic medications: May reduce hypoglycemic effect; monitor blood glucose NSAIDs: Increased risk of GI adverse effects Potassium-depleting agents: Enhanced hypokalemic effectAdverse Effects
Common adverse reactions (≥10%):- Cushingoid appearance
- Weight gain
- Vitamin D deficiency
- Hirsutism
- Irritability
- Acne
- Adrenal insufficiency
- Immunosuppression and increased infection risk
- Hypertension
- Osteoporosis and fractures
- Gastrointestinal perforation
- Ophthalmic effects (cataracts, glaucoma)
- Neuropsychiatric reactions
Monitoring Parameters
- Height and weight (at each visit)
- Blood pressure (regularly)
- Bone mineral density (baseline and annually)
- Ophthalmologic examinations (annually)
- Serum glucose and electrolytes (periodically)
- Growth velocity in pediatric patients
- Signs and symptoms of infection
- Adrenal function tests when indicated
- Vitamin D levels
Patient Education
- Take medication exactly as prescribed with food
- Do not stop taking abruptly; dosage must be tapered under medical supervision
- Report any signs of infection (fever, sore throat, fatigue)
- Monitor weight regularly and report rapid weight gain
- Report vision changes or eye pain
- Inform all healthcare providers about vamorolone use
- Carry medical identification indicating steroid use
- Report mood changes, depression, or emotional disturbances
- Maintain adequate calcium and vitamin D intake
- Avoid contact with individuals who have contagious illnesses
- Discuss vaccination schedule with healthcare provider
References
1. FDA Prescribing Information: Vamorolone Oral Suspension (2023) 2. Conklin LS, et al. Phase IIa trial in Duchenne muscular dystrophy shows vamorolone is a first-in-class dissociative steroidal anti-inflammatory drug. Pharmacol Res. 2018;136:140-150. 3. Hoffman EP, et al. Vamorolone trial in Duchenne muscular dystrophy shows dose-related improvement of muscle function. Neurology. 2019;93(13):e1312-e1323. 4. Mah JK, et al. Long-term effects of glucocorticoids on function, quality of life, and survival in patients with Duchenne muscular dystrophy: a prospective cohort study. Lancet. 2018;391(10119):451-461. 5. ClinicalTrials.gov: Safety and Efficacy of Vamorolone in Boys With Duchenne Muscular Dystrophy (NCT03439670) 6. Guglieri M, et al. Efficacy and safety of vamorolone in Duchenne muscular dystrophy: An 18-month interim analysis of a randomized controlled trial. Neuromuscul Disord. 2022;32(7):555-565.